Proteomic analysis shows down-regulations of cytoplasmic carbonic anhydrases, CAI and CAII, are early events of colorectal carcinogenesis but are not correlated with lymph node metastasis

Aim The aim of the study was to screen the markedly down-regulated proteins in colorectal cancer and analyze their relationship to carcinogenesis, cancer progression and pathological aspects. Methods Proteomic analysis was preformed on six fresh colorectal cancer tissues and paired normal colorectal mucosa by two-dimensional differential gel electrophoresis and matrix-assisted laser desorption/ionization-time of flight mass spectrometry. Two markedly down-regulated proteins among the proteins, of which the expressions were significantly decreased in colorectal cancer compared to normal mucosa, were confirmed by Western Blot in 12 colorectal cancers. Their relationship to carcinogenesis, cancer progression and pathological aspects of colorectal cancer were analyzed in 64 colorectal cancer and paired normal mucosa, 27 benign polyps, and 20 lymph node metastases by immunohistochemistry. Results Two-dimensional differential gel electrophoresis analysis showed there were 2 protein spots, of which the average abundances decreased 3.62 and 3.76 fold in colorectal cancer compared to normal mucosa, respectively. They were identified by matrix-assisted laser desorption/ionization-time of flight mass spectrometry as carbonic anhydrase I and II (CAI and CAII). Validation by Western Blot in 12 colorectal cancers showed there were significantly different expressions of CAI and CAII between colorectal cancer and normal mucosa (P = 0.002 and 0.027, respectively). Immunohistochemistry analysis indicated the expression of CAI and CAII was decreased from normal mucosa to benign polyps, and to colorectal cancer stepwise significantly (P <0.05). However, there were no differences in their expressions between lymph node metastasis and colorectal cancer (P >0.05). There were decreasing trends of CAI and CAII expressions from well to poor differentiation and from stage I or II to stage III or IV, but they were not statistically significant (P >0.05). Conclusions CAI and CAII are necessary enzymes of the colorectum for their normal function. Down-regulations of CAI and CAII are early events of colorectum carcinogenesis. They have no correlations with lymph node metastasis.

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Effect of brain-derived neurotrophic factor/TrkB axis on cancer progression in colorectal cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.e14039 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. e14039-e14039

Author(s):

Yasuhiro Inoue ◽

Yoshinaga Okugawa ◽

Susumu Saigusa ◽

Junichiro Hiro ◽

Yuji Toiyama ◽

...

Keyword(s):

Colorectal Cancer ◽

Lymph Node ◽

Lymph Node Metastasis ◽

Cancer Cells ◽

Cancer Progression ◽

Hepatic Metastasis ◽

Neurotrophic Factor ◽

Brain Derived Neurotrophic Factor ◽

Mrna Levels ◽

Node Metastasis

e14039 Background: Brain-derived neurotrophic factor (BDNF) is one of the member of the neurotropin family known to activate the high affinity tyrosine kinase B (TrkB) receptor together with the pan-neurotropin low-affinity coreceptor p75 (p75NTR). TrkB activation by BDNF has been shown to facilitate the progression of several cancers, however, no reports have shown the clinical and biological effects of BDNF/TrkB axis expression in colorectal cancer(CRC). Methods: A total of 223 consecutive patients undergoing surgery for CRC were enrolled. We analyzed BDNF/TrkB mRNA levels by real-time reverse transcription PCR in CRC tissues, and their relationships with clinicopathological findings including survival were investigated. BDNF and TrkB expression were also evaluated by immunohistochemistry. To investigate the biological role of the BDNF/TrkB axis, recombinant human BDNF and Trk antagonist K252a were used for proliferation, migration, and anoikis assays in CRC cell lines. Results: The mean BDNF level in CRC tissue was 94.3 (0-1326.8). One hundred five of 223 patients (47.1%) showed detectable BDNF levels, whereas the remainder had no detectable. BDNF positive expression was significantly associated with undifferenciated histological type, lymph node metastasis, and hepatic metastasis. In addition, increased BDNF/TrkB axis expression associated with lymph node metastasis, hepatic metastasis, and peritoneal disseamination. Immunohistochemical analysis indicated intense BDNF expression in the cytoplasm of cancer cells, and intense TrkB expression in the nuclei of cancer cells, respectively. In vitro, administration of recombinant human BDNF promoted proliferation, anoikis resistance, and partial migration. These effects were generally inhibited by Trk antagonist K252a. Conclusions: We demonstrated the clinical and biological function of BDNF/TrkB axis in CRC. BDNF/TrkB axis appears to play an important role in cancer progression, and blocking this pathway might be clinically useful in developing therapies for patients with CRC.

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Landscape of Genome-Wide DNA Methylation of Colorectal Cancer Metastasis

Cancers ◽

10.3390/cancers12092710 ◽

2020 ◽

Vol 12 (9) ◽

pp. 2710

Author(s):

Carmen Ili ◽

Kurt Buchegger ◽

Hannah Demond ◽

Juan Castillo-Fernandez ◽

Gavin Kelsey ◽

...

Keyword(s):

Colorectal Cancer ◽

Dna Methylation ◽

Lymph Node ◽

Lymph Node Metastasis ◽

Cancer Progression ◽

Cancer Metastasis ◽

Cpg Island ◽

The Cancer Genome Atlas ◽

Node Metastasis ◽

Genome Wide

Colorectal cancer is a heterogeneous disease caused by both genetic and epigenetics factors. Analysing DNA methylation changes occurring during colorectal cancer progression and metastasis formation is crucial for the identification of novel epigenetic markers of patient prognosis. Genome-wide methylation sequencing of paired samples of colon (normal adjacent, primary tumour and lymph node metastasis) showed global hypomethylation and CpG island (CGI) hypermethylation of primary tumours compared to normal. In metastasis we observed high global and non-CGI regions methylation, but lower CGI methylation, compared to primary tumours. Gene ontology analysis showed shared biological processes between hypermethylated CGIs in metastasis and primary tumours. After complementary analysis with The Cancer Genome Atlas (TCGA) cohort, FIGN, HTRA3, BDNF, HCN4 and STAC2 genes were found associated with poor survival. We mapped the methylation landscape of colon normal tissues, primary tumours and lymph node metastasis, being capable of identified methylation changes throughout the genome. Furthermore, we found five genes with potential for methylation biomarkers of poor prognosis in colorectal cancer patients.

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Upregulated CNTN1 is associated with lymph node metastasis and poor prognosis of colorectal cancer

Cancer Biomarkers ◽

10.3233/cbm-190981 ◽

2020 ◽

pp. 1-9

Author(s):

Guangyao Li ◽

Zhengjun Zhang ◽

Guochao Ge ◽

Ke Fang ◽

Jianyu Zhu

Keyword(s):

Colorectal Cancer ◽

Lymph Node ◽

Lymph Node Metastasis ◽

Tumor Development ◽

Normal Mucosa ◽

Clinical Analysis ◽

Immunoglobulin Superfamily ◽

Node Metastasis ◽

Adjacent Normal Mucosa ◽

Potential Biomarker

BACKGROUND: Contactin1 (CNTN1), a member of the immunoglobulin superfamily, is known to correlate with tumor development and progression. Although recent studies have found that elevated CNTN1 has been demonstrated in some types of cancers, the expression and prognosis of CNTN1 in colorectal cancer (CRC) are unclear. Here, we aimed to determine the clinicopathological characteristics and prognostic role of CNTN1 in CRC patients. METHODS: The protein expression of CNTN1 in tumor tissues was evaluated by immunohistochemistry. In addition, the mRNA and protein expressions of CNTN1 were examined by qRT-PCR and Western blotting analysis in 40 matched adjacent normal mucosa samples. The relationships of CNTN1 with clinicopathological data and prognosis significance were analyzed. RESULTS: Immunohistochemical consequence suggested that the protein level of CNTN1 was obviously raised in CRC compared with adjacent normal mucosa tissues (56.9% vs 10.3%, P< 0.05). In addition, we detected a significant increase in CNTN1 mRNA and protein levels in CRC tissues compared with the matched adjacent normal mucosa tissues. Moreover, increased CNTN1 exprssion was significantly associated with tumor size, lymph node metastasis (LNM), tumor node-metastasis (TNM) stage and carcino-embryonic antigen (CEA) in clinical analysis. Kaplan-Meier analysis suggested that patients with CNTN1 over-expression showed worse overall survival (OS) (P= 0.001). Multivariate analysis indicated that high CNTN1 expression was an independent predictor for poor OS in CRC patients (P= 0.028). Further analysis revealed that patients with high CNTN1 combined with LNM present accurately predicted poorer outcome. CONCLUSION: Taken together, the findingsindicate that CNTN1 plays a significant role and serve as a potential biomarker for the prediction of adverse prognosis in CRC. Intriguingly, high express of CNTN1 + LNM-present combination may improve the accuracy of prognosis.

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Microenvironmental markers are correlated with lymph node metastasis in invasive submucosal colorectal cancer

Histopathology ◽

10.1111/his.14388 ◽

2021 ◽

Author(s):

Tamotsu Sugai ◽

Noriyuki Yamada ◽

Mitsumasa Osakabe ◽

Mai Hashimoto ◽

Noriyuki Uesugi ◽

...

Keyword(s):

Colorectal Cancer ◽

Lymph Node ◽

Lymph Node Metastasis ◽

Node Metastasis ◽

Submucosal Colorectal Cancer

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Increased Expression of VANGL1 is Predictive of Lymph Node Metastasis in Colorectal Cancer: Results from a 20-Gene Expression Signature

Journal of Personalized Medicine ◽

10.3390/jpm11020126 ◽

2021 ◽

Vol 11 (2) ◽

pp. 126

Author(s):

Noshad Peyravian ◽

Stefania Nobili ◽

Zahra Pezeshkian ◽

Meysam Olfatifar ◽

Afshin Moradi ◽

...

Keyword(s):

Gene Expression ◽

Colorectal Cancer ◽

Lymph Node ◽

Lymph Node Metastasis ◽

Candidate Genes ◽

Case Series ◽

Gene Expression Signature ◽

Gene Panel ◽

Expression Levels ◽

Node Metastasis

This study aimed at building a prognostic signature based on a candidate gene panel whose expression may be associated with lymph node metastasis (LNM), thus potentially able to predict colorectal cancer (CRC) progression and patient survival. The mRNA expression levels of 20 candidate genes were evaluated by RT-qPCR in cancer and normal mucosa formalin-fixed paraffin-embedded (FFPE) tissues of CRC patients. Receiver operating characteristic curves were used to evaluate the prognosis performance of our model by calculating the area under the curve (AUC) values corresponding to stage and metastasis. A total of 100 FFPE primary tumor tissues from stage I–IV CRC patients were collected and analyzed. Among the 20 candidate genes we studied, only the expression levels of VANGL1 significantly varied between patients with and without LNMs (p = 0.02). Additionally, the AUC value of the 20-gene panel was found to have the highest predictive performance (i.e., AUC = 79.84%) for LNMs compared with that of two subpanels including 5 and 10 genes. According to our results, VANGL1 gene expression levels are able to estimate LNMs in different stages of CRC. After a proper validation in a wider case series, the evaluation of VANGL1 gene expression and that of the 20-gene panel signature could help in the future in the prediction of CRC progression.

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16. Apical lymph node metastasis and survival in resected colorectal cancer

Pathology ◽

10.1097/01.pat.0000461625.51675.14 ◽

2015 ◽

Vol 47 ◽

pp. S105

Author(s):

Nav Gill ◽

Christopher W. Toon ◽

Nicole Watson ◽

Anthony J. Gill

Keyword(s):

Colorectal Cancer ◽

Lymph Node ◽

Lymph Node Metastasis ◽

Node Metastasis

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Tumor Budding and Pathological Differentiation Are Predictive Markers for Lymph Node Metastasis in T1 Colorectal Cancer

Gastrointestinal Endoscopy ◽

10.1016/j.gie.2006.03.538 ◽

2006 ◽

Vol 63 (5) ◽

pp. AB216 ◽

Cited By ~ 1

Author(s):

Hitoshi Yamauchi ◽

Kazutomo Togashi ◽

Hiroshi Kawamura ◽

Junichi Sasaki ◽

Masaki Okada ◽

...

Keyword(s):

Colorectal Cancer ◽

Lymph Node ◽

Lymph Node Metastasis ◽

Predictive Markers ◽

Tumor Budding ◽

Node Metastasis ◽

Pathological Differentiation ◽

T1 Colorectal Cancer

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Pure Well-Differentiated Adenocarcinoma Is a Safe Factor for Lymph Node Metastasis in T1 and T2 Colorectal Cancer: A Pilot Study

Gastroenterology Research and Practice ◽

10.1155/2018/8798405 ◽

2018 ◽

Vol 2018 ◽

pp. 1-9 ◽

Cited By ~ 2

Author(s):

Naohisa Yoshida ◽

Masayoshi Nakanishi ◽

Ken Inoue ◽

Ritsu Yasuda ◽

Ryohei Hirose ◽

...

Keyword(s):

Colorectal Cancer ◽

Lymph Node ◽

Lymph Node Metastasis ◽

Venous Invasion ◽

Lymphatic Invasion ◽

Clinicopathological Factors ◽

Node Metastasis ◽

Kappa Value ◽

T1 And T2 ◽

Well Differentiated

Background and Aims. Various risk factors for lymph node metastasis (LNM) have been reported in colorectal T1 cancers. However, the factors available are insufficient for predicting LNM. We therefore investigated the utility of the new histological factor “pure well-differentiated adenocarcinoma” (PWDA) as a safe factor for predicting LNM in T1 and T2 cancers. Materials and Methods. We reviewed 115 T2 cancers and 202 T1 cancers in patients who underwent surgical resection in our center. We investigated the rates of LNM among various clinicopathological factors, including PWDA. PWDA was defined as a lesion comprising only well-differentiated adenocarcinoma. The consistency of the diagnosis of PWDA was evaluated among two pathologists. In addition, 72 T1 cancers with LNM from 8 related hospitals over 10 years (2008–2017) were also analyzed. Results. The rates of LNM and PWDA were 23.5% and 20.0%, respectively, in T2 cancers. Significant differences were noted between patients with and without LNM regarding lymphatic invasion (81.5% vs. 36.4%, p<0.001), poor histology (51.9% vs. 19.3%, p=0.008), and PWDA (3.7% vs. 25.0%, p=0.015). The rates of LNM and PWDA were 8.4% and 36.1%, respectively, in T1 cancers. Regarding the 73 PWDA cases and 129 non-PWDA cases, the rates of LNM were 0.0% and 13.2%, respectively (p<0.001). Among the 97 cases with lymphatic or venous invasion, the rates of LNM in 29 PWDA cases and 68 non-PWDA were 0% and 14.7%, respectively (p=0.029). The agreement of the two pathologists for the diagnosis of PWDA was acceptable (kappa value > 0.5). A multicenter review showed no cases of PWDA among 72 T1 cancers with LNM. Conclusions. PWDA is considered to be a safe factor for LNM in T1 cancer.

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